1. Technical Field of the Invention
The present invention relates, as novel and useful industrial products, to a novel class of compounds which are modulators of the Peroxisome Proliferator-Activated Receptor (PPAR) type receptors. This invention also relates to their method of preparation and to their formulation into pharmaceutical compositions for administration in human or veterinary medicine, or, alternatively, into cosmetic compositions.
2. Description of Background and/or Related and/or Prior Art
The activity of the PPAR-type receptors has been the subject of numerous studies. There may be mentioned, as a guide, the publication entitled “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes During the Differentiation of Human Keratinocytes”, Michel Rivier et al., J. Invest. Dermatol., 111, 1998, p. 1116-1121, in which a large number of bibliographic references relating to PPAR-type receptors is listed. There may also be mentioned, as a guide, the dossier entitled “The PPARs: From Orphan Receptors to Drug Discovery”, Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach, and Brad R. Henke, J. Med. Chem., 2000, Vol. 43, p. 527-550.
The PPAR receptors activate transcription by binding to elements of DNA sequences, called peroxisome proliferator response elements (PPRE), in the form of a heterodimer with the retinoid X receptors (called RXRs).
Three human PPAR subtypes have been identified and described: PPARα, PPARγ and PPARδ (or NUC1). PPARα is mainly expressed in the liver while PPARδ is ubiquitous.
It is described in WO 98/32444 that PPARα selective compounds play a role in the barrier function and the differentiation of the stratum corneum.
PPARγ is the most widely studied of the three subtypes. All the references suggest a critical role of the PPARγ receptors in the regulation of differentiation of adipocytes, where it is highly expressed. It also plays a key role in systemic lipid homeostasis.
It has in particular been described in WO 96/33724 that PPARγ-selective compounds, such as prostaglandin-J2 or -D2, are potential active agents for treating obesity and diabetes.